Understanding the economic feasibility of cross-laminated timber (CLT), an emerging and sustainable alternative to concrete and steel, is critical for the rapid expansion of the mass timber industry. However, previous studies on economic performance of CLT have not fully considered the variations in the feedstock, plant capacities, manufacturing parameters, and capital and operating costs. This study fills this gap by developing a techno-economic analysis of producing CLT panels in the Southern United States. The effects of those variations on minimum selling price (MSP) of CLT panels are explored by Monte Carlo simulation. The results show that, across all the plant capacities from 30,000 to 150,000 m3/year, the MSP ranges from $345 to $609/m3 with a ±6%–9% range caused by the variations in feedstocks, key manufacturing parameters, capital and operating cost. The MSP decreases significantly along the increasing capacities. A sensitivity analysis exhibits that the lumber price, lumber preparing loss, plant capacity, and the installed costs of layering and gluing, finishing, and miscellaneous, are the top driving factors to CLT MSP. Supported by Geographic Information System, this study also studies the transportation cost of delivering CLT to customers under three CLT demanding levels (1%, 5%, 15%). The results show that the transportation cost is 1%–8% of the MSP. Lower demanding level or higher plant capacity can increase the transportation cost due to average longer delivering distance. When considering the delivered cost that sums MSP and transportation cost, larger plant capacity does not necessarily generate lower delivered cost.